Structured, multicomponent, community-based programme for women's health and infant health and development in rural Vietnam: a parallel-group cluster randomised controlled trial.

BACKGROUND: Interventions to improve early childhood development have previously addressed only one or a few risk factors. Learning Clubs is a structured, facilitated, multicomponent programme designed to address eight potentially modifiable risk factors, and offered from mid-pregnancy to 12 months post partum; we aimed to establish whether this programme could improve the cognitive development of children at 2 years of age. METHODS: For this parallel-group cluster-randomised controlled trial, 84 of 116 communes (the clustering unit) in HaNam Province in rural Vietnam were randomly selected and randomly assigned to receive the Learning Clubs intervention (n=42) or usual care (n=42). Women aged at least 18 years who were pregnant (gestational age <20 weeks) were eligible for inclusion. Data sources were standardised, and study-specific questionnaires assessing risks and outcomes were completed in interviews in mid-pregnancy (baseline), late pregnancy (after 32 weeks of gestation), at 6-12 months post partum, and at the end of the study period when children were 2 years of age. Mixed-effects models were used to estimate trial effects, adjusting for clustering. The primary outcome was the cognitive development of children at 2 years of age, assessed by the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III) cognitive score. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000442303). FINDINGS: Between April 28, 2018, and May 30, 2018, 1380 women were screened and 1245 were randomly assigned (669 to the intervention group and 576 to the control group). Data collection was completed on Jan 17, 2021. Data at the end of the study period were contributed by 616 (92%) of 669 women and their children in the intervention group, and by 544 (94%) of 576 women and their children in the control group. Children aged 2 years in the intervention group had significantly higher mean Bayley-III cognitive scores than those in the control group (99·6 [SD 9·7] vs 95·6 [9·4]; mean difference 4·00 [95% CI 2·56-5·43]; p<0·0001). At 2 years of age, 19 (3%) children in the intervention group had Bayley-III scores less than 1 SD, compared with 32 (6%) children in the control group, but this difference was not significant (odds ratio 0·55 [95% CI 0·26-1·17]; p=0·12). There were no significant differences between groups in maternal, fetal, newborn, or child deaths. INTERPRETATION: A facilitated, structured, community-based, multicomponent group programme improved early childhood development to the standardised mean in rural Vietnam and could be implemented in other similarly resource-constrained settings. FUNDING: Australian National Health and Medical Research Council and Grand Challenges Canada Saving Brains Initiative. TRANSLATION: For the Vietnamese translation of the abstract see Supplementary Materials section.

How much of the effect of disability acquisition on mental health is mediated through employment and income? A causal mediation analysis quantifying interventional indirect effects using data from four waves of an Australian cohort study.

OBJECTIVES: There is evidence that disability acquisition causes a decline in mental health, but few studies have examined the causal mechanisms through which the effect operates. This study used a novel approach to mediation analysis to quantify interventional indirect effects (IIEs) through employment and income. DESIGN AND SETTING: We used four waves of longitudinal data (2011-2014) from the Household, Income and Labour Dynamics in Australia Survey, a nationally representative survey of Australian households. PARTICIPANTS: Working aged individuals who acquired a disability (n=233) were compared with those who remained disability-free in all four waves (n=5419). PRIMARY OUTCOME MEASURE: Self-reported mental health was measured using the Mental Health Inventory subscale of the Short Form 36 general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being. STATISTICAL ANALYSIS: We conducted a causal mediation analysis quantifying IIEs of disability acquisition on mental health operating through two distinct mediators: employment status and income. We used multiple imputation with 50 imputed datasets to account for missing data. RESULTS: The total causal effect of disability acquisition on mental health was estimated to be a 4.8-point decline in mental health score (estimated mean difference: -4.8, 95% CI -7.0 to -2.7). The IIE through employment was estimated to be a 0.5-point difference (-0.5, 95% CI -1.0 to 0.0), accounting for 10.6% of the total effect, whereas there was no evidence that income explained any of the effects. CONCLUSIONS: This study estimated that disability-related mental health inequalities could be reduced by 10.6% if employment rates were the same for people with disability as those without disability. The results suggest that employment is implicated in the relationship between disability acquisition and mental health and that more research is needed to understand the influence of other aspects of employment and other socioeconomic characteristics.

The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia.

The widespread use of primaquine (PQ) radical cure for P. vivax, is constrained by concerns over its safety. We used routinely collected patient data to compare the overall morbidity and mortality in patients treated with and without PQ without prior testing of Glucose-6-Phosphate-Dehydrogenase (G6PD) deficiency in Papua, Indonesia, where there is a low prevalence of G6PD deficiency. Records were collated from patients older than 1 year, with P. vivax infection, who were treated with an artemisinin combination therapy (ACT). The risks of re-presentation, hospitalization, major fall in haemoglobin and death within 30 days were quantified and compared between patients treated with and without PQ using a Cox regression model. In total 26,216 patients with P. vivax malaria presented to the hospital with malaria during the study period. Overall 27.56% (95% Confidence Interval (95%CI): 26.96-28.16) of 21,344 patients treated with PQ re-presented with any illness within 30 days and 1.69% (1.51-1.88) required admission to hospital. The corresponding risks were higher in the 4,872 patients not treated with PQ; Adjusted Hazard Ratio (AHR) = 0.84 (0.79-0.91; p<0.001) and 0.54 (0.41-0.70; p<0.001) respectively. By day 30, 14.15% (12.45-16.05) of patients who had received PQ had a fall in haemoglobin (Hb) below 7g/dl compared to 20.43% (16.67-24.89) of patients treated without PQ; AHR = 0.66 (0.45-0.97; p = 0.033). A total of 75 (0.3%) patients died within 30 days of treatment with a mortality risk of 0.27% (0.21-0.35) in patients treated with PQ, compared to 0.38% (0.24-0.60) without PQ; AHR = 0.79 (0.43-1.45; p = 0.448). In Papua, Indonesia routine administration of PQ radical cure without prior G6PD testing, was associated with lower risk of all cause hospitalization and other serious adverse clinical outcomes. In areas where G6PD testing is not available or cannot be delivered reliably, the risks of drug induced haemolysis should be balanced against the potential benefits of reducing recurrent P. vivax malaria and its associated morbidity and mortality.

Does the effect of disability acquisition on mental health differ by employment characteristics? A longitudinal fixed-effects analysis.

PURPOSE: Longitudinal studies have suggested a causal relationship between disability acquisition and mental health, but there is substantial heterogeneity in the magnitude of the effect. Previous studies have provided evidence that socioeconomic characteristics can buffer the effect but have not examined the role of employment characteristics. METHODS: We used data from 17 annual waves of the Household, Income and Labour Dynamics in Australia Survey to compare the mental health of working age individuals before and after disability acquisition, using the Mental Health Inventory, a subscale of the SF-36 health questionnaire. Linear fixed-effects regression models were used to estimate the effect of disability acquisition on mental health. We tested for effect modification by two characteristics of people's employment prior to disability acquisition: occupational skill level and contract type. Multiple imputation using chained equations was used to handle missing data. RESULTS: Disability acquisition was associated with a substantial decline in mental health score (estimated mean difference: - 4.3, 95% CI - 5.0, - 3.5). There was evidence of effect modification by occupational skill level, with the largest effects seen for those in low-skilled jobs (- 6.1, 95% CI - 7.6, - 4.5), but not for contract type. CONCLUSIONS: The findings highlight the need for social and health policies that focus on increasing employment rates, improving the sustainability of employment, and providing employment services and education and training opportunities for people who acquire a disability, particularly for people in low-skilled occupations, to reduce the mental health inequalities experienced by people with disabilities.

Early and late mortality after malaria in young children in Papua, Indonesia.

BACKGROUND: In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown. METHODS: Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods. RESULTS: In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis; 6184 (39.3%) with Plasmodium falciparum, 7499 (47.7%) with P. vivax, 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections. Within 1 year, 48.4% (7620/15,716) of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307-1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896-944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 [0.69,1.49]) or between 31 and 365 days (HR = 1.30 [0.90,1.88]). Children who died had a greater incidence of malaria, 2280 [95%CI 1946-2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124-1158] per 1000 patient years in those surviving. CONCLUSIONS: Children under-5 years old with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in this vulnerable population.

Multiple imputation methods for handling missing values in a longitudinal categorical variable with restrictions on transitions over time: a simulation study.

BACKGROUND: Longitudinal categorical variables are sometimes restricted in terms of how individuals transition between categories over time. For example, with a time-dependent measure of smoking categorised as never-smoker, ex-smoker, and current-smoker, current-smokers or ex-smokers cannot transition to a never-smoker at a subsequent wave. These longitudinal variables often contain missing values, however, there is little guidance on whether these restrictions need to be accommodated when using multiple imputation methods. Multiply imputing such missing values, ignoring the restrictions, could lead to implausible transitions. METHODS: We designed a simulation study based on the Longitudinal Study of Australian Children, where the target analysis was the association between (incomplete) maternal smoking and childhood obesity. We set varying proportions of data on maternal smoking to missing completely at random or missing at random. We compared the performance of fully conditional specification with multinomial and ordinal logistic imputation, and predictive mean matching, two-fold fully conditional specification, indicator based imputation under multivariate normal imputation with projected distance-based rounding, and continuous imputation under multivariate normal imputation with calibration, where each of these multiple imputation methods were applied, accounting for the restrictions using a semi-deterministic imputation procedure. RESULTS: Overall, we observed reduced bias when applying multiple imputation methods with restrictions, and fully conditional specification with predictive mean matching performed the best. Applying fully conditional specification and two-fold fully conditional specification for imputing nominal variables based on multinomial logistic regression had severe convergence issues. Both imputation methods under multivariate normal imputation produced biased estimates when restrictions were not accommodated, however, we observed substantial reductions in bias when restrictions were applied with continuous imputation under multivariate normal imputation with calibration. CONCLUSION: In a similar longitudinal setting we recommend the use of fully conditional specification with predictive mean matching, with restrictions applied during the imputation stage.

Do material, psychosocial and behavioural factors mediate the relationship between disability acquisition and mental health? A sequential causal mediation analysis.

BACKGROUND: There is evidence of a causal relationship between disability acquisition and poor mental health; however, the mechanism by which disability affects mental health is poorly understood. This gap in understanding limits the development of effective interventions to improve the mental health of people with disabilities. METHODS: We used four waves of data from the Household, Income and Labour Dynamics in Australia Survey (2011-14) to compare self-reported mental health between individuals who acquired any disability (n=387) and those who remained disability-free (n=7936). We tested three possible pathways from disability acquisition to mental health, examining the effect of material, psychosocial and behavioural mediators. The effect was partitioned into natural direct and indirect effects through the mediators using a sequential causal mediation analysis approach. Multiple imputation using chained equations was used to assess the impact of missing data. RESULTS: Disability acquisition was estimated to cause a five-point decline in mental health [estimated mean difference: -5.3, 95% confidence interval (CI) -6.8, -3.7]. The indirect effect through material factors was estimated to be a 1.7-point difference (-1.7, 95% CI -2.8, -0.6), explaining 32% of the total effect, with a negligible proportion of the effect explained by the addition of psychosocial characteristics (material and psychosocial: -1.7, 95% CI -3.0, -0.5) and a further 5% by behavioural factors (material-psychosocial-behavioural: -2.0, 95% CI -3.4, -0.6). CONCLUSIONS: The finding that the effect of disability acquisition on mental health operates predominantly through material rather than psychosocial and behavioural factors has important implications. The results highlight the need for better social protection, including income support, employment and education opportunities, and affordable housing for people who acquire a disability.

Disability acquisition and mental health: effect modification by demographic and socioeconomic characteristics using data from an Australian longitudinal study.

OBJECTIVES: There is evidence of a causal relationship between disability acquisition and poor mental health, but the substantial heterogeneity in the magnitude of the effect is poorly understood and may be aetiologically informative. This study aimed to identify demographic and socioeconomic factors that modify the effect of disability acquisition on mental health. DESIGN AND SETTING: The Household, Income and Labour Dynamics in Australia Survey is a nationally representative longitudinal survey of Australian households that has been conducted annually since 2001. Four waves of data were included in this analysis, from 2011 to 2014. PARTICIPANTS: Individuals who acquired a disability (n=387) were compared with those who remained disability-free in all four waves (n=7936). PRIMARY OUTCOME MEASURE: Mental health was measured using the mental health subscale of the Short Form 36 (SF-36) general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being. METHODS: Linear regression models were fitted to estimate the effect of disability acquisition on mental health, testing for effect modification by key demographic and socioeconomic characteristics. To maximise causal inference, we used a propensity score approach with inverse probability of treatment weighting to control for confounding and multiple imputation using chained equations to assess the impact of missing data. RESULTS: On average, disability acquisition was associated with a 5-point decline in mental health score (estimated mean difference: -5.1, 95% CI -7.2 to -3.0). There was strong evidence that income and relationship status modified the effect, with more detrimental effects in the lowest (-12.5, 95% CI -18.5 to -6.5) compared with highest income quintile (-1.1, 95% CI -4.9 to 2.7) and for people not in a relationship (-8.8, 95% CI -12.9 to -4.8) compared with those who were (-3.7, 95% CI -6.1 to -1.4). CONCLUSIONS: Our results suggest that the detrimental effect of disability acquisition on mental health is substantially greater for socioeconomic disadvantaged individuals.

A comparison of multiple imputation methods for handling missing values in longitudinal data in the presence of a time-varying covariate with a non-linear association with time: a simulation study.

BACKGROUND: Missing data is a common problem in epidemiological studies, and is particularly prominent in longitudinal data, which involve multiple waves of data collection. Traditional multiple imputation (MI) methods (fully conditional specification (FCS) and multivariate normal imputation (MVNI)) treat repeated measurements of the same time-dependent variable as just another 'distinct' variable for imputation and therefore do not make the most of the longitudinal structure of the data. Only a few studies have explored extensions to the standard approaches to account for the temporal structure of longitudinal data. One suggestion is the two-fold fully conditional specification (two-fold FCS) algorithm, which restricts the imputation of a time-dependent variable to time blocks where the imputation model includes measurements taken at the specified and adjacent times. To date, no study has investigated the performance of two-fold FCS and standard MI methods for handling missing data in a time-varying covariate with a non-linear trajectory over time - a commonly encountered scenario in epidemiological studies. METHODS: We simulated 1000 datasets of 5000 individuals based on the Longitudinal Study of Australian Children (LSAC). Three missing data mechanisms: missing completely at random (MCAR), and a weak and a strong missing at random (MAR) scenarios were used to impose missingness on body mass index (BMI) for age z-scores; a continuous time-varying exposure variable with a non-linear trajectory over time. We evaluated the performance of FCS, MVNI, and two-fold FCS for handling up to 50% of missing data when assessing the association between childhood obesity and sleep problems. RESULTS: The standard two-fold FCS produced slightly more biased and less precise estimates than FCS and MVNI. We observed slight improvements in bias and precision when using a time window width of two for the two-fold FCS algorithm compared to the standard width of one. CONCLUSION: We recommend the use of FCS or MVNI in a similar longitudinal setting, and when encountering convergence issues due to a large number of time points or variables with missing values, the two-fold FCS with exploration of a suitable time window.

Antenatal Iron Supplementation Regimens for Pregnant Women in Rural Vietnam and Subsequent Haemoglobin Concentration and Anaemia among Their Infants.

BACKGROUND: Little evidence about the effects of antenatal iron supplementation on infant anaemia is available. The aim was to compare effects on six-month-old infants' Haemoglobin (Hb) concentration and anaemia of daily iron-folic acid (IFA), twice-weekly IFA with or without other micronutrients (MMN) and usual antenatal care in rural Vietnam. METHODS AND FINDINGS: Secondary data analysis from: a prospective population-based observational study (OS) which examined effects of antenatal psychosocial factors, anaemia and iron deficiency on infant development and health; and a three-arm cluster randomised trial (CRT) of different antenatal iron supplementation regimens. In the OS 497 women (<20 weeks gestation) from 50 randomly-selected communes participated, and in the CRT 1,258 pregnant women (<16 weeks gestation) in 104 communes were allocated randomly to trial arms. The main outcome was six-month-old infant Hb concentration. Baseline data included women's socio-demographic characteristics, reproductive health, Hb and serum ferritin. Mean differences in infant Hb and odds ratios of infant anaemia between CRT arms and OS were calculated by multivariable regression models, controlling for baseline differences and clustering, using robust standard errors. Infant anaemia prevalence was 68.6% in the OS, 47.2% daily IFA, 53.5% weekly IFA, and 50.3% MMN conditions. After adjustment, mean infant haemoglobin levels in daily IFA (mean difference = 0.95 g/dL; 95%CI 0.7-11.18); weekly IFA (0.91; 95%CI 0.69-1.12) and MMN (1.04; 95%CI 0.8-1.27) were higher than in the OS. After adjustment there were lower odds ratios of anaemia among infants in the daily IFA (OR = 0.31; 95% CI 0.22-0.43), weekly IFA (0.38; 95%CI 0.26-0.54) and MMN (0.33; 95%CI 0.23-0.48) groups than in the OS. CONCLUSIONS: Infant anaemia is a public health problem in Vietnam and other resource-constrained countries. All supplementation regimens could have clinically significant benefits for Hb and reduce anaemia risk among six-month-old infants. Universal provision of free intermittent iron supplements is warranted.

Perinatal common mental disorders among women and the social and emotional development of their infants in rural Vietnam.

BACKGROUND: Little is known about the effect of common mental disorders (CMD) among women in the perinatal period on infant development in low-income countries. The aim of this study was to examine the effect of exposures to maternal symptoms of ante- and post-natal CMD on infant social-emotional development in a low-income setting. METHODS: A prospective community-based investigation in which a cohort of pregnant women was recruited in rural northern Vietnam and followed until 6 months postpartum. Psychosocial and biological data were collected in four assessment waves. The outcome was 6-month old infants' scores on the Bayley Scales of Infant and Toddler Development Social-Emotional Questionnaire. Direct and indirect effects of maternal CMD on the outcome were tested simultaneously with path analysis. RESULTS: Complete data were available for 378 mother-infant dyads. There were no direct effects of ante- or post-natal CMD on infant Social-Emotional scores. However, there was an indirect pathway (path coefficient -1.11, 95% CI -1.79 to -0.42) in which antenatal CMD were associated with increased likelihood of postnatal CMD, which were associated with reduced parenting self-efficacy and less affectionate and warm parenting practices, which were associated with lower infant social-emotional scores. Parenting self-efficacy and practices also mediated the adverse effects of a woman being young or of high parity or experiencing poverty, intimate partner violence, a poor relationship with her own mother, non-economic life adversity and insufficient breastmilk, on infant social-emotional development. LIMITATIONS: We acknowledge some limitations including (1) a moderate rate of attrition, (2) the use of a screening test for perinatal CMD, (3) the Bayley scales are not yet validated for use in Vietnam and (4) possible response bias in which maternal perceptions of their infants were influenced by their mood. CONCLUSIONS: These data indicate that women's antenatal and postnatal mental health is a crucial but currently inadequately understood determinant of the social and emotional development of infants in low-income settings.

Impact on infants' cognitive development of antenatal exposure to iron deficiency disorder and common mental disorders.

OBJECTIVES: The aim of this study was to examine the effects of antenatal exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on cognitive development of 6 months old infants in a developing country. METHODS: A prospective population-based study in a rural province in Vietnam, which enrolled pregnant women at 12-20 weeks gestation and followed them up with their infants until six months postpartum. Criteria for IDA were Hb <11 g/dL and serum ferritin <15 ng/mL. CMD symptoms were assessed by the Edinburgh Postnatal Depression Scale-Vietnam validation. Infant cognitive development was assessed by Bayley Scales of Infant and Toddler Development, 3rd Ed. Path analyses were performed to determine the direct and indirect, partly or fully mediated, causal effects of the antenatal exposures. RESULTS: A total of 497 pregnant women were recruited, of those 378 women provided complete data which were included in the analyses. Statistically significant direct adverse effects of persistent antenatal IDA (estimated difference of -11.62 points; 95% CI -23.01 to -0.22) and antenatal CMD (-4.80 points; 95% CI: -9.40 to -0.20) on infant Bayley cognitive scores at six months were found. Higher birthweight, household wealth, and self-rated sufficient supply of breastmilk were associated with higher cognitive scores. Maternal age >30 years and primiparity had an indirect adverse effect on infants' Bayley cognitive scores. CONCLUSIONS: These findings suggest that antenatal IDA and CMD both have adverse effects on child cognitive development, which if unrecognized and unaddressed are likely to be lasting. It is crucial that both these risks are considered by policy makers, clinicians, and researchers seeking to improve child cognitive function in developing countries.

Psychological and social factors associated with late pregnancy iron deficiency anaemia in rural Viet Nam: a population-based prospective study.

OBJECTIVES: The aim of this study was to examine the relationships between psychological and social factors and late pregnancy IDA among pregnant women in rural Viet Nam. METHODS: Pregnant women from 50 randomly-selected communes within Ha Nam province were recruited and assessed at 12 - 20 weeks gestation (Wave 1, W1). They were followed up in the last trimester (Wave 2, W2). IDA was defined as Haemoglobin < 11 g/dL and serum ferritin < 15 ng/mL. Symptoms of Common Mental Disorders (CMD) were assessed by the Edinburgh Postnatal Depression Scale-Vietnam (EPDS-V). Persistent antenatal CMD was defined as having an EPDS-V score ≥ 4 in both W1 and W2. Hypothesis models were tested by Structural Equation Modeling analyses. RESULTS: A total of 378 women provided complete data at both W1 and W2. The incidence risk of IDA in the third trimester was 13.2% (95% confidence interval (CI): 9.8-16.7). Persistent CMD was found in 16.9% (95% CI: 13.1-20.7) pregnant women and predicted by intimate partner violence, fear of other family members, experience of childhood abuse, coincidental life adversity, and having a preference for the sex of the baby. There was a significant pathway from persistent CMD to IDA in late pregnancy via the length of time that iron supplements had been taken. Receiving advice to take iron supplements and higher household wealth index were indirectly related to lower risk of late pregnancy IDA. Early pregnancy IDA and being multi-parous also contributed to late pregnancy IDA. CONCLUSIONS: Antenatal IDA and CMD are prevalent public health problems among women in Viet Nam. The link between them suggests that while direct recommendations to use iron supplements are important, the social factors associated with common mental disorders should be addressed in antenatal care in order to improve the health of pregnant women and their infants.

Effectiveness of a targeted exercise intervention in reversing older people's mild balance dysfunction: a randomized controlled trial.

BACKGROUND: Previous research has mainly targeted older people with high risk of falling. The effectiveness of exercise interventions in older people with mild levels of balance dysfunction remains unexplored. OBJECTIVE: This study evaluated the effectiveness of a home balance and strength exercise intervention in older people systematically screened as having mild balance dysfunction. DESIGN: This was a community-based, randomized controlled trial with assessors blinded to group allocation. PARTICIPANTS: Study participants were older people who reported concerns about their balance but remained community ambulant (n=225). After a comprehensive balance assessment, those classified as having mild balance dysfunction (n=165) were randomized into the trial. INTERVENTION: Participants in the intervention group (n=83) received a 6-month physical therapist-prescribed balance and strength home exercise program, based on the Otago Exercise Program and the Visual Health Information Balance and Vestibular Exercise Kit. Participants in the control group (n=82) continued with their usual activities. OUTCOME MEASURES: Laboratory and clinical measures of balance, mobility, and strength were assessed at baseline and at a 6-month reassessment. RESULTS: After 6 months, the intervention group (n=59) significantly improved relative to the control group (n=62) for: the Functional Reach Test (mean difference=2.95 cm, 95% confidence interval [CI]=1.75 to 4.15), the Step Test (2.10 steps/15 seconds, 95% CI=1.17 to 3.02), hip abductor strength (0.02, 95% CI=0.01 to 0.03), and gait step width (2.17 cm, 95% CI=1.23 to 3.11). There were nonsignificant trends for improvement on most other measures. Fourteen participants in the intervention group (23.7%) achieved balance performance within the normative range following the exercise program, compared with 3 participants (4.8%) in the control group. LIMITATIONS: Loss to follow-up (26.6%) was slightly higher than in some similar studies but was unlikely to have biased the results. CONCLUSIONS: A physical therapist-prescribed home exercise program targeting balance and strength was effective in improving a number of balance and related outcomes in older people with mild balance impairment.

A simplified intravenous artesunate regimen for severe malaria.

BACKGROUND: We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria. METHODS: This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed. RESULTS: In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008). CONCLUSIONS: Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children. CLINICAL TRIALS REGISTRATION: NCT00522132.

Meat consumption and risk of primary hip and knee joint replacement due to osteoarthritis: a prospective cohort study.

BACKGROUND: There is emerging evidence for a beneficial effect of meat consumption on the musculoskeletal system. However, whether it affects the risk of knee and hip osteoarthritis is unknown. We performed a prospective cohort study to examine the relationship between meat consumption and risk of primary hip and knee replacement for osteoarthritis. METHODS: Eligible 35,331 participants were selected from the Melbourne Collaborative Cohort Study recruited during 1990-1994. Consumption of fresh red meat, processed meat, chicken, and fish was assessed using a food frequency questionnaire. Primary hip and knee replacement for osteoarthritis during 2001-2005 was determined by linking the cohort records to the Australian National Joint Replacement Registry. RESULTS: There was a negative dose-response relationship between fresh red meat consumption and the risk of hip replacement (hazard ratio (HR) 0.94 per increase in intake of one time/week, 95% confidence interval (CI) 0.89-0.98). In contrast, there was no association with knee replacement risk (HR 0.98, 95% CI 0.94-1.02). Consumption of processed meat, chicken and fish were not associated with risk of hip or knee replacement. CONCLUSION: A high level consumption of fresh red meat was associated with a decreased risk of hip, but not knee, joint replacement for osteoarthritis. One possible mechanism to explain these differential associations may be via an effect of meat intake on bone strength and hip shape. Further confirmatory studies are warranted.

Is physical activity a risk factor for primary knee or hip replacement due to osteoarthritis? A prospective cohort study.

OBJECTIVE: To estimate prospectively any association between measures of physical activity and the risk of either primary knee or hip replacement due to osteoarthritis (OA). METHODS: Eligible subjects (n = 39,023) were selected from participants in a prospective cohort study recruited 1990-1994. Primary knee and hip replacement for OA during 2001-2005 was determined by linking the cohort records to the National Joint Replacement Registry. A total physical activity level was computed, incorporating both intensity and frequency for different forms of physical activity obtained by questionnaire at baseline attendance. RESULTS: There was a dose-response relationship between total physical activity level and the risk of primary knee replacement [hazards ratio (HR) 1.04, 95% CI 1.01-1.07 for an increase of 1 level in total physical activity]. Although vigorous activity frequency was associated with an increased risk of primary knee replacement (HR 1.42, 95% CI 1.08-1.86) for 1-2 times/week and HR 1.24 (95% CI 0.90-1.71) for ≥ 3 times/week), the p for trend was marginal (continuous HR 1.08, 95% CI 1.00-1.16, p = 0.05). The frequency of less vigorous activity or walking was not associated with the risk of primary knee replacement, nor was any measure of physical activity associated with the risk of primary hip replacement. CONCLUSION: Increasing levels of total physical activity are positively associated with the risk of primary knee but not hip replacement due to OA. Physical activity might affect the knee and hip joints differently depending on the preexisting health status and anatomy of the joint, as well as the sort of physical activity performed.

Relationship between body adiposity measures and risk of primary knee and hip replacement for osteoarthritis: a prospective cohort study.

INTRODUCTION: Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. It is unknown whether the adipose mass and the distribution of adipose mass are associated with the risk of primary knee and hip replacement for osteoarthritis. The aim of the present investigation was to examine this in a cohort study. METHODS: A total of 39,023 healthy volunteers from Melbourne, Australia were recruited for a prospective cohort study during 1990 to 1994. Their body mass index, waist circumference, and waist-to-hip ratio were obtained from direct anthropometric measurements. The fat mass and percentage fat were estimated from bioelectrical impedance analysis. Primary knee and hip replacements for osteoarthritis between 1 January 2001 and 31 December 2005 were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) for primary joint replacement associated with each adiposity measure. RESULTS: Comparing the fourth quartile with the first, there was a threefold to fourfold increased risk of primary joint replacement associated with body weight (HR = 3.44, 95% confidence interval (CI) = 2.83 to 4.18), body mass index (HR = 3.44, 95% CI = 2.80 to 4.22), fat mass (HR = 3.51, 95% CI = 2.87 to 4.30), and percentage fat (HR = 2.99, 95% CI = 2.46 to 3.63). The waist circumference (HR = 2.77, 95% CI = 2.26 to 3.39) and waist-to-hip ratio (HR = 1.46, 95% CI = 1.21 to 1.76) were less strongly associated with the risk. Except for the waist-to-hip ratio, which was not significantly associated with hip replacement risk, all adiposity measures were associated with the risk of both knee and hip joint replacement, and were significantly stronger risk factors for knee. CONCLUSIONS: Risk of primary knee and hip joint replacement for osteoarthritis relates to both adipose mass and central adiposity. This relationship suggests both biomechanical and metabolic mechanisms associated with adiposity contribute to the risk of joint replacement, with stronger evidence at the knee rather than the hip.